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Abstract Objective Patients with mild oral and maxillofacial space infection (OMSI) usually need only antimicrobial therapy. However, surgical intervention is eventually needed after using antibiotics for a period. The objective of this study was to explore the risk factors for drug therapy failure in OMSI. Subjects and methods A retrospective case‒control study was designed. From August 2020 to September 2022, patients at Shanghai Jiao Tong University Affiliated Ninth People’s Hospital who were diagnosed with OMSI were retrospectively reviewed. The outcome variable was surgical intervention after the use of antibiotics. We collected common biological factors, including demographic characteristics, routine blood test results, C-reactive protein (CRP) levels and composite indicators, such as neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR). The χ2 test and binary logistic regression were used to examine the association between biological factors and the outcome variable. Results Forty-six patients were included in this study. Further surgical intervention was needed in 20 patients (43.5%). The NLR showed a significant association with further surgical drainage (p = 0.01). A binary logistic regression equation was found by using stepwise regression based on the Akaike information criterion (R2 = 0.443), which was associated with sex (odds ratio [OR], 0.216; p = 0.092), NLR (OR, 1.258; p = 0.045), red blood cell (RBC) count (OR, 4.372; p = 0.103) and monocyte (MONO) count (OR, 9.528, p = 0.023). Receiver operating characteristic analysis produced an area under the curve for NLR of 0.725 (p = 0.01) and for the binary logistic regression model of 0.8365 (p

Background/purpose: The diagnosis and treatment of Sjogren's syndrome (SS) are commonly conducted by rheumatologists and stomatologists. The purpose of this study was to compare the scientometric characteristics of SS publications by rheumatologists and stomatologists. Materials and methods: All the papers on cheilitis were comprehensively retrieved from the Scopus database, and divided into rheumatologists and stomatologists groups. Results: There were 3245 and 1209 papers on SS were published by rheumatologists and stomatologists, respectively. For the most-cited top-200 papers, the total citation count was 29,764 and the h index was 108 for SS publications by rheumatologists; whereas the count is 19,891 and h index is 81 for publications by stomatologists. Interestingly, we observed that accumulated citations of the publications by stomatologists cooperated with rheumatologists were larger than those by stomatologists alone during 2012–2022. The more common keywords such as saliva, salivation, minor salivary glands, parotid gland, submandibular gland, sialography, lip, dental caries, and hyposalivation were reported by stomatologists. The more frequent keywords such as rheumatoid factor, fatigue, lymphoma, interstitial lung disease, arthralgia, Raynaud phenomenon, lymphadenopathy, and vasculitis were reported by rheumatologists. Conclusion: This study firstly reports the scientometric characteristics of SS publications by rheumatologists and stomatologists. The scale and citations of rheumatologists' publications greatly outweigh those of stomatologists, suggesting stomatologists can cooperate more with rheumatologists regarding SS research.

Abstract In this study, we prepared a bionic nanosystem of trastuzumab-functionalized SK-BR-3 cell membrane hybrid liposome-coated pyrotinib (Ptb-M-Lip-Her) for the treatment of HER2-positive breast cancer. Transmission electron microscopy, dynamic light scattering, polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting were used to verify the successful preparation of Ptb-M-Lip-Her. In vitro drug release experiments proved that Ptb-M-Lip-Her had a sustained release effect. Cell uptake experiments and in vivo imaging experiments proved that Ptb-M-Lip-Her had good targeting ability to homologous tumor cells (SK-BR-3). The results of cell experiments such as MTT, flow cytometry, immunofluorescence staining and in vivo antitumor experiments showed that Ptb-M-Lip-Her could significantly promote apoptosis and inhibit the proliferation of SK-BR-3 cells. These results clearly indicated that Ptb-M-Lip-Her may be a promising biomimetic nanosystem for targeted therapy of HER2-positive breast cancer.

Angelica dahurica root (ADR), a commonly utilized herbal medicine in China and other Asian nations, which has anti-inflammatory effects on diverse inflammatory ailments. However, the bioactive components and underlying mechanism responsible for the anti-inflammatory effect of ADR are still unclear. This work attempted to discover the anti-inflammatory bioactive compounds and explore their underlying mechanism in ADR based on spectrum-effect relationship analysis and NF-κB signaling pathway. Chromatographic fingerprints of ADR samples were established by high performance liquid chromatography with diode array detection (HPLC-DAD), and a total of eleven common peaks were selected. Then, high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC-Q/TOF-MS) was employed for identification of eleven common peaks in ADR Meanwhile, the anti-inflammatory activities of ADR samples were assessed by inhibition of NO, interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) production in LPS-induced RAW264.7 cells. The spectrum-effect relationships between the eleven common peaks in HPLC fingerprints and anti-inflammatory effects of ADR samples were investigated to identify the potential anti-inflammatory bioactive compounds by grey relational analysis (GRA) and partial least squares regression (PLSR). The spectrum-effect relationship analysis results indicated that six coumarin compounds, including bergapten, xanthotoxin, phellopterin, isoimperatorin, xanthotoxol and imperatorin could be potential anti-inflammatory bioactive compounds in ADR. The further validation experiments also showed that these six coumarins demonstrated significant inhibition of NO, IL-1β, IL-6, and TNF-α production in LPS-induced RAW264.7 cells. In addition, western blot analysis was conducted to explore the mechanisms of two potential anti-inflammatory bioactive compounds (phellopterin and isoimperatorin) by assessing the protein levels in the NF-κB signaling pathway. The western blot results illustrated that phellopterin and isoimperatorin could significantly down-regulate the phosphorylated NF-κB p65 (p-p65), phosphorylated IκBα (p-IκBα) and iNOS, and depress the pro-portion of p-p65/p65 and p-IκBα/IκBα, which indicated that these two coumarins in ADR could potentially exert anti-inflammatory effects by suppressing of NF-κB pathway.

There is a growing amount of research that highlights the significant connection between the development of colitis and both metabolic imbalance and the inflammatory response. Tagatose, an inherent sweetening agent and alternative to sugar, plays a crucial role in the biosynthesis of several chemicals and metabolic pathways in living organisms. However, the specific biochemical mechanism via which tagatose hinders colitis is still not understood. According to recent study, tagatose plays a crucial role in safeguarding the integrity of tight junctions inside the intestinal mucosal barrier. Furthermore, it is crucial to acknowledge the presence of a correlation between the severity of inflammatory bowel disease (IBD) and the occurrence of colorectal cancer (CRC), chemically-induced colitis in rodents, and reduced blood levels of tagatose. The treatment of tagatose resulted in a decrease in intestinal mucosal injury in mice with colitis, regardless of whether it was caused by dextran sodium sulfate (DSS) or spontaneous colitis in IL-10-/- mice and C3H/HeJBir mice. The introduction of tagatose in a colitis model triggers a cascade of events, wherein it hinders the expulsion of cathepsin B and enhances lysosomal cohesiveness. The aforementioned method successfully inhibits the activity of myosin light chain kinase (MLCK) in the context of intestinal epithelial damage, hence impeding the deterioration of tight junction integrity and the initiation of mitochondrial dysfunction. In summary, the outcomes of the study have provided empirical evidence that substantiates the beneficial effects of tagatose in mitigating the progression of colitis. The ability to prevent the disruption of the intestinal barrier is responsible for this achievement. Hence, tagatose has promise as a therapeutic adjunct for the management of colitis.

Abstract Enhancing both the number of active sites available and the intrinsic activity of Co‐based electrocatalysts simultaneously is a desirable goal. Herein, a ZIF‐67‐derived hierarchical porous cobalt sulfide decorated by Au nanoparticles (NPs) (denoted as HP‐Au@CoxSy@ZIF‐67) hybrid is synthesized by low‐temperature sulfuration treatment. The well‐defined macroporous–mesoporous–microporous structure is obtained based on the combination of polystyrene spheres, as‐formed CoxSy nanosheets, and ZIF‐67 frameworks. This novel three‐dimensional hierarchical structure significantly enlarges the three‐phase interfaces, accelerating the mass transfer and exposing the active centers for oxygen evolution reaction. The electronic structure of Co is modulated by Au through charge transfer, and a series of experiments, together with theoretical analysis, is performed to ascertain the electronic modulation of Co by Au. Meanwhile, HP‐Au@CoxSy@ZIF‐67 catalysts with different amounts of Au were synthesized, wherein Au and NaBH4 reductant result in an interesting “competition effect” to regulate the relative ratio of Co2+/Co3+, and moderate Au assists the electrochemical performance to reach the highest value. Consequently, the optimized HP‐Au@CoxSy@ZIF‐67 exhibits a low overpotential of 340 mV at 10 mA cm–2 and a Tafel slope of 42 mV dec–1 for OER in 0.1 M aqueous KOH, enabling efficient water splitting and Zn–air battery performance. The work here highlights the pivotal roles of both microstructural and electronic modulation in enhancing electrocatalytic activity and presents a feasible strategy for designing and optimizing advanced electrocatalysts.

The issue of urban resilience plays great significance and value for the sustainable development of cities, which has attracted increasing attention from scholars and governments, especially in the western region of China. Based on the Production-Living-Ecological (PLE) system, this study attempts to describe urban resilience by the combination system that contains with P,L,E subsystem. The integrated approach including FAHP-EM,GRA-TOPSIS, CCDM, and ODM is proposed to reveal the urban resilience level and seek out the key constraints' indicators. Then, an empirical analysis of panel data of 18 cities in Sichuan Province from 2011 to 2021 was conducted to analyze the development process. The valuation results suggested that:(1)for urban resilience level, most cities at the moderate imbalance level and basically maintained at this level, only Chengdu is reaching the basic coordination level since in 2013.(2)The insufficient development of P,L,E subsystem is the reason for the moderate imbalance development, especially the key limiting factor is the P subsystem's low development level.(3)the most prominent obstacle indicators are x1(per capita local financial expenditure on science and technology), x2(per capita of R&D spending), x8(total export-import per capita), x14(number of people with basic medical insurance), x22(length of urban drainage pipeline), x23(number of public toilets per person) and the contribution values reach 7.56%,7.49%,11.02%, 9.14%,12.53%, 12.60% respectively. The detailed reference suggestions and effective measures put forwarded for policy makers and planners to promote urban resilience in Western China.

Abstract Background Dendrobium officinale Kimura et Migo (D. officinale) is a well-known traditional Chinese medicine with high content polysaccharides in stems. The SWEET (Sugars Will Eventually be Exported Transporters) family is a novel class of sugar transporters mediating sugar translocation among adjacent cells of plants. The expression patterns of SWEETs and whether they are associated with stress response in D. officinale remains uncovered. Results Here, 25 SWEET genes were screened out from D. officinale genome, most of which typically contained seven transmembrane domains (TMs) and harbored two conserved MtN3/saliva domains. Using multi-omics data and bioinformatic approaches, the evolutionary relationship, conserved motifs, chromosomal location, expression patterns, correlationship and interaction network were further analyzed. DoSWEETs were intensively located in nine chromosomes. Phylogenetic analysis revealed that DoSWEETs were divided into four clades, and conserved motif 3 specifically existed in DoSWEETs from clade II. Different tissue-specific expression patterns of DoSWEETs suggested the division of their roles in sugar transport. In particular, DoSWEET5b, 5c, and 7d displayed relatively high expression levels in stems. DoSWEET2b and 16 were significantly regulated under cold, drought, and MeJA treatment, which were further verified using RT-qPCR. Correlation analysis and interaction network prediction discovered the internal relationship of DoSWEET family. Conclusions Taken together, the identification and analysis of the 25 DoSWEETs in this study provide basic information for further functional verification in D. officinale.

Background/purpose: Metagenomic next-generation sequencing (mNGS) has been widely used for the detection of pathogens causing infectious diseases. This study aimed to evaluate the potential ability of mNGS to detect pathogens causing oral and maxillofacial space infection (OMSI) and compare the results with those of the traditional diagnostic microbial culture method. Materials and methods: We retrospectively reviewed the data of 218 patients diagnosed with OMSI who underwent microbial culture and mNGS at the Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, from July 2020 to January 2022. Results: The positivity rate of mNGS (216 cases) was significantly higher than that of microbial culture (123 cases). The most frequently detected bacteria were different between these two detection methods. Streptococcus constellatus (16.05%, 35), Streptococcus anginosus (15.69%, 34) and Klebsiella pneumoniae (6.88%, 15) were the most commonly isolated bacteria by culture. However, Peptostreptococcus stomatis (61.47%, 134), Parvimonas micra (68.35%, 149) and Streptococcus constellatus (57.34%, 125) were the most commonly detected bacteria by mNGS. mNGS also has advantages in diagnosing viral infections. The optimal numbers of diagnostic reads were 1162 and 588 for the diagnosis of Streptococcus anginosus and Streptococcus constellatus infections, respectively. Read numbers were significantly correlated with C-reactive protein (CRP), procalcitonin (PCT), and blood glucose levels and neutrophil percentage (NEUT%). Conclusion: For pathogens causing OMSI, mNGS had a higher rate of microbial pathogen detection and remarkable advantages in identifying coinfections involving viruses and fungi. The read numbers for mNGS are important for diagnostic accuracy and disease severity evaluation.

Abstract Background The aging of the population is a social problem faced by many countries in the world. With the increase in the elderly population, the number of patients with Kummell’s disease is also gradually increasing. No study has demonstrated that Kummell’s disease has a clear correlation with the foramen of a vertebrobasilar vein. Objectives The research was conducted to describe and evaluate the morphological characteristics of a basivertebral foramen in patients with osteoporosis and Kummell’s disease by CT; to infer whether the specific morphological characteristics of basivertebral foramen may be one of the risk factors of Kummell’s disease; to provide clinical suggestions for the treatment of Kummell’s disease. Design Retrospective analysis from January 2020 to December 2021 on 83 patients with 83 vertebral bodies (T8-L5) diagnosed with senile osteoporosis and Kummell’s disease hospitalized in our hospital due to chronic low back pain, including 57 women and 23 men. Group A was assigned for the following patients: the age ranged from 59 to 86 years old, with the average age of 67.30 ± 7.32 years old; the body mass index ranged from 20.01 to 29.46 kg/m2, with the average body mass index of 23.51 ± 3.03 kg/m2.Group B was assigned for the following patients: 83 patients diagnosed with senile osteoporosis in our outpatient department from January 2020 to December 2021, including 41 males and 42 females; the age ranged from 60 to 85 years, with an average age of 68.52 ± 4.68 years old; the height to weight ratio met the normal reference standard (except 20% above or 10% below the standard weight). Through the lanwon PACS imaging system, the related parameters of the vertebrobasilar foramen in patients with osteoporosis and Kummell’s disease were measured to evaluate and analyze the correlation between the morphological characteristics of the vertebrobasilar foramen in patients with osteoporosis and Kummell’s disease. Results In patients with osteoporosis, the distribution of incidence rate of Kummell’s disease in the spine was consistent with that of osteoporotic compression fractures. Sagittal view of the vertebral body on CT scan and the triangular-shaped, trapezoidal-shaped, and irregular-shaped basivertebral foramen in group A accounted for 18%,57%,and 36%,respectively. In group B, triangular-shaped, trapezoidal-shaped, and irregular-shaped foramen accounted for 51%,17%,and 26%,respectively.The distribution of triangular-shaped, trapezoidal-shaped, and irregular-shaped foramen was compared between groups A and B, and the difference was recorded as statistically significant (P 0.05).On a horizontal CT scan of the vertebra of group A, triangles, trapezoids, and irregularities accounted for 28%, 26%, and 47%, respectively. In group B, triangles,trapezoids,and irregularities accounted for 31%, 37%, and 30%, respectively. The difference in the distribution of the triangular-shaped and trapezoidal-shaped foramen in groups A and B was statistically insignificant (P > 0.05), while that of irregular-shaped was statistically significant (P 0.05) in the difference in the morphological distribution of triangular-shaped and trapezoidal-shaped foramen in group A, while that of irregular-shaped was found to be statistically significant (P 0.05).In general, about 8% of the vertebral body of BF has an osseous septum. In group A, 97% are single-holed while the remaining 3% are porous; in group B, those with single holes accounted for 76%, while the remaining 24% are porous. In groups A and B, the difference in the morphological distribution of single-holed and multi-holed T8, T11, T12, L1, L2, L4, and L5 vertebral bodies was statistically significant (P

The quality of rice, evaluated using multiple quality-related traits, is the main determinant of its market competitiveness. In this study, two japonica rice varieties with significant differences in quality-related traits were used as parents to construct two populations, BC3F2 and BC3F2:3, with Kongyu131 (KY131) as the recurrent parent. A genetic linkage map was constructed using the BC3F2 population based on 151 pairs of SSR/InDel polymorphic markers selected between the parents. Grain-shape-related traits (grain length GL, grain width GW, and length-to-width ratio LWR), chalkiness-related traits (white-core rate WCR, white-belly rate WBR, white-back rate BR, and chalkiness rate CR), and amylose content (AC) were investigated in the two populations in 2017 and 2018. Except for BR and CR, the traits showed similar characteristics with a normal distribution in both populations. Genetic linkage analysis was conducted for these quality-related traits, and a total of 37 QTLs were detected in the two populations. Further validation was performed on the newly identified QTLs with larger effects, and three grain shape QTLs and four chalkiness QTLs were successfully validated in different environments. One repeatedly validated QTL, qWCR3, was selected for fine mapping and was successfully narrowed down to a 100 kb region in which only two genes, LOC_0s03g45210 and LOC_0s03g45320, exhibited sequence variations between the parents. Furthermore, the variation of LOC_Os03g45210 leads to a frameshift mutation and premature protein termination. The results of this study provide a theoretical basis for positional cloning of the qWCR3 gene, thus offering new genetic resources for rice quality improvement.

Increasing evidence indicates that inflammatory cytokines are involved in the pathogenesis of recurrent aphthous stomatitis (RAS). A wide range of over ten cytokines in peripheral blood of RAS patients have been investigated in different studies. Yet, which of the ones are the most prominent indicators contributed for the process of RAS are uncertain. Herein, a total of 16 eligible case–control studies including 1051 cases of RAS and 616 health controls were summarized. The bubble chart analysis showed that the most prominent cytokines for RAS were interleukin (IL)-6 (646 cases, 308 controls), TNF-α (498 cases, 298 controls), and IL-2 (371 cases, 264 controls). On the other hand, 9 studies on cytokines as therapeutic indicators of RAS were identified. The effect of levamisole and thalidomide on cytokines mainly were IL-6, TNF-α, and IL-8. Collectively, an optimum panel of IL-6, TNF-α, and IL-2 maybe serve as the potential significant indicators for RAS investigations.

Abstract Aim To review and analyse the evidence on the efficacy and safety of non‐pharmacological interventions for preterm infants to relieve endotracheal suctioning (ES) pain. Design A systematic review per the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. Methods Six databases were searched with a retrieval strategy. Parallel and crossover randomized controlled trials reporting non‐pharmacological interventions for relieving ES pain in preterm infants were identified from inception to 1 September 2021. The protocol was published in PROSPERO (CRD42021276058). Results Ten studies were retrieved, including nine different non‐pharmacological interventions. Seven studies reported that non‐pharmacological interventions in relieving pain were more effective than conventional care during ES, and three trials reported its safety. Due to the heterogeneity of pain assessment tools, time of assessment and population, only Facilitated tucking had sufficient evidence that it is a safe and effective non‐pharmacological intervention.

The by-products obtained after the extraction of vitamin B2 from fermented soybean (VBP), primarily consisting of soybean meal, soybean oil, vitamin B2, and Bacillus subtilis, may serve as a cost-effective and recycled resource in animal feed. This research aimed to assess the impact of VBP on the growth performance, nutrient utilization, blood parameters, and meat quality of pigs in the growing–finishing phase. In this 16-week feeding experiment, 140 pigs of mixed breed [Duroc × (Landrace × Yorkshire)] were used, with an initial average body weight of 26.05 ± 1.32 kg. The pigs were assigned randomly to one of four dietary groups, each consisting of five pigs, with two gilts and three barrows per pen, and a total of seven repetitions per treatment. The animals were fed different levels of by-products after vitamin B2 extraction (0, 10, 20, and 30 g/kg as the CON, VBP10, VBP20, and VBP30 dietary groups, respectively) in a three-phase feeding trial (wk. 0–4, 4–8, and 8–13). When higher levels of VBP were added as supplements, the outcomes indicated that there were no notable variations (p > 0.05) in growth performance and nutrient digestibility among the treatment groups throughout the trial. In phase II (4–8 weeks), the inclusion of VBP in the diets showed a reduction (p = 0.011; with linear and quadratic effects, p = 0.003) in serum norepinephrine concentration. The sensory evaluation of meat color was linearly improved (p = 0.043) in pigs fed with graded levels of VBP supplementation. The percentage of lean meat showed a significant improvement (p = 0.016) with the gradual levels of VBP supplementation. The addition of 30 g/kg (on an as-fed basis) of vitamin B2 by-products in the diet can simultaneously mitigate the negative impacts of acute stress without compromising growth performance and enhance the percentage of lean meat. These findings suggest that VBP could be a viable and economical alternative to corn and soybean meal and partially replace it in pig feed.

Scientometric analysis of a disease is often conducted to recognize research hotspots and investigate latest trends. In this brief report, we provide a scientometric overview of oral cancer research in Taiwan and mainland China. There were 1924 and 3853 articles on oral cancer research originating from Taiwan and mainland China, respectively. In Taiwan, the risk factors including areca/betel quid chewing, tobacco smoking, and alcohol use were the distinctive keywords. For basic research, genotype, reactive oxygen, p53, mitochondria and caspase-9 were the distinctive keywords. In mainland China, experiment methods such as genetic transfection, gene silencing, colony formation, tumor xenograft were the distinctive keywords. Epithelial mesenchymal transition, long untranslated RNA, protein function, uvomorulin, and Bcl-2 were the distinctive keywords of basic research. Collectively, we hope that these scientometric characteristics will aid clinicians and researchers for obtaining information on oral cancer and can be of guidance for future studies.

Scientometric analysis of a disease is often conducted to recognize research trends and study hotspots. In this report, we analyze the scientometric characteristics of oral potentially malignant disorder (OPMD) research in Taiwan and mainland China. There are 324 and 718 articles on OPMD research originating from Taiwan and Mainland between 2006 and 2021, respectively. The most common subtype of OPMD research in Taiwan and Mainland is oral submucous fibrosis and lichen planus, respectively. Based on the list of main keywords extracted from the included articles, areca/betel quid chewing and alcohol use are the distinctive risk factors in Taiwan. Research on cancer screening, fibroblast/myofibroblast, and smooth muscle actin α are distinctive keywords in Taiwan; whereas the research on apoptosis, cytokine, and inflammation are distinctive keywords in Mainland. The distinctive characteristics of OPMD research are analyzed between Taiwan and mainland China, which may reflect the importance and concerned topics of research.

ObjectiveTo explore the effect of the family-centered empowerment model (FECM) on reducing anxiety, improving care ability, and readiness for hospital discharge of main caregivers of preterm infants.MethodsThe primary caregivers of preterm infants who were admitted to the Neonatal intensive care Unit (NICU) of our center from September 2021 to April 2022 were selected as the research objects. According to the wishes of the primary caregivers of preterm infants, they were divided into group A (FECM group) and group B (non-FECM group). The intervention effects were evaluated with the Anxiety Screening Scale (GAD-7), the Readiness for Hospital Discharge Scale-Parent Version (RHDS-Parent Form), and the Primary Caregivers of Premature Infants Assessment of Care Ability Questionnaire.ResultsBefore the intervention, there was no statistically significant difference in the general information, anxiety screening, the scores of each dimension, and total score of the comprehensive ability of the main caregivers, and the score of caregiver preparedness between the two groups (P > 0.05). After the intervention, there were statistically significant differences in the anxiety screening, the total score and total score of each dimension of the care ability, and the score of caregiver preparedness between the two groups (P

Chemotherapy is one of the main therapeutic strategies for the treatment of malignant melanoma. Conventional chemotherapeutic agents often lack targeting abilities, and efficacy is hampered by their high toxic effects to normal tissues and rapid clearance from the circulation. In this study, porous paclitaxel (PTX)-loaded polylactide (PLA) microspheres (PPMSs) were prepared by a modified double-emulsion-solvent evaporation method. In addition, PPMSs and cisplatin (DDP) were co-embedded in a thermosensitive hydrogel to construct a dual-drug co-delivery hydrogel system (PPMSs/DDP@Gel) for in-situ chemotherapy to treat melanoma by means of an intra-tumoral injection. The system allows for the sustained release of two drugs and exhibits good temperature-sensitive properties. In vitro antitumor activity showed that this hydrogel composite can induce B16 cell apoptosis and inhibit its migration. In vivo, anti-tumor studies have shown that the PPMSs/DDP@Gel significantly inhibited tumor growth, prolonged the survival of tumor-bearing mice, and had no obvious toxic side effects on major organs. Furthermore, immunohistochemical analysis revealed that PPMSs/DDP@Gel significantly inhibited tumor cell proliferation and promoted apoptosis of tumor cells. Taken together, the injectable temperature-sensitive PPMSs/DDP@Gel is a promising candidate for the local treatment of melanoma.

Abstract Local hypoxia is a common feature of many solid tumors and may lead to unsatisfactory chemotherapy outcomes. Anaerobic bacteria that have an affinity to hypoxic areas can be used to achieve targeted drug delivery in tumor tissues. In this study, we developed a biocompatible bacteria/nanoparticles biohybrid (Bif@DOX-NPs) platform that employs the anaerobic Bifidobacterium infantis (Bif) to deliver adriamycin-loaded bovine serum albumin nanoparticles (DOX-NPs) into breast tumors. The Bif@DOX-NPs retained the targeting ability of B. infantis to hypoxic regions, as well as the cytotoxicity of DOX. The biohybrids were able to actively colonize the hypoxic tumors and significantly increased drug accumulation at the tumor site. The DOX concentration in the tumor masses colonized by Bif@DOX-NPs was 4 times higher than that in the free DOX-treated tumors, which significantly prolonged the median survival of the tumor-bearing mice to 69 days and reduced the toxic side-effects of DOX. Thus, anaerobic bacteria-based biohybrids are a highly promising tool for the targeted treatment of solid tumors with inaccessible hypoxic regions. Graphical Abstract

Previous studies have shown that abnormal metabolic reprogramming in CD4+ T cells could explain the occurrence of several autoimmune disorders, including Sjogren’s syndrome (SS). However, therapeutic targets of the abnormal metabolism of CD4+ T cells remain to be explored. Here, we report that glutaminase 1 (Gls1), a pivotal factor in glutaminolysis, might be involved in the pathogenesis of SS. The expression of Gls1 was upregulated in infiltrated labial CD4+ T cells and circulating CD4+ T cells of SS patients. Inhibiting Gls1 with BPTES significantly abolished the proliferation rate, as indicated by EdU, CFSE, and Western blot analyses. Additionally, BPTES downregulated the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) values of activated CD4+ T cells from SS mice. In vivo, we injected different doses of BPTES into SS-like NOD/Ltj mice and found that 10 mg/kg BPTES significantly restored the salivary flow rate. Histological and qRT–PCR analyses showed that this concentration of BPTES attenuated lymphocytic infiltration and the numbers of PCNA-positive cells and CD4+ T cells. The proportions of IFNγ-producing cells and IL-17A-producing cells and the expression of several proinflammatory cytokines, including IFNγ and IL-17A, were also affected in the salivary glands of SS-like mice. Cytokine production in circulating serum was analyzed and showed that BPTES downregulated the effector functions of Th17 cells and Th1 cells. Collectively, these results indicate a positive relationship between Gls1 and SS development. Pharmacological inhibition of Gls1 with BPTES could normalize the effector functions of CD4+ T cells and effectively attenuate the symptoms of SS.

Conserved regions of the antibody molecule impact its downstream biological effects. Here the authors show that a rigid hinge conformation increases the agonistic activity of CD40 and DR5 antibodies, distinctly from FcγR-binding, suggesting that the hinge and FcR binding regions can be separately modified to optimize therapies.

Rice (Oryza sativa L.) chalkiness greatly reduces the rice quality and the commercial value. In this study, qWCR4, a previously reported quantitative trait locus (QTL) of white-core rate (WCR), was confirmed by a BC5F2 segregation population and further fine mapped to a 35.26 kb region. In the qWCR4 region, LOC_Os04g50060 and LOC_Os04g50070 showed significant differences in expression level in endosperm between two NILs, whereas four other genes had no expression. Starch granules in the central endosperm of chalky grains from NIL(J23B) with higher WCR exhibited a typically round and loosely packed morphology. NIL(J23B) with higher WCR accompanied a higher seed filling speed. Moreover, qWCR4J23B (qWCR4 allele in J23B) increased WCR, grain numbers per plant, seed setting rate, grain width, and thousand-grain weight, contributing to a superior yield per plant. All in all, our research results not only lay a foundation for map-based cloning of qWCR4 but also provide new genetic resources for rice yield and quality breeding.

POEMS syndrome is a rare multisystem disease associated with an underlying plasma cell disorder. Its name is an acronym for peripheral neuropathy (P), endocrinopathy (E), organomegaly (O), monoclonal plasma cell proliferative disorder (M), and skin changes (S). This case report describes a patient with POEMS syndrome who presented with progressive fatigue and numbness in the lower extremities. Initially, the patient was erroneously diagnosed with diabetes and diabetic peripheral neuropathy because of the endocrinopathy associated with POEMS syndrome. After a second hospitalization, the patient was diagnosed with POEMS syndrome and recovered with alkylator therapy and a peripheral blood stem cell transplant. The patient’s overall condition was improved at the 1-year follow-up. POEMS syndrome should be considered if a patient presents with endocrinopathy and unexplained peripheral neuropathy.

Acute myeloid leukemia (AML) is an aggressive haematological malignancy characterized by highly proliferative accumulation of immature and dysfunctional myeloid cells. Quercetin (Qu), one kind of flavonoid, exhibits anti-cancer property in multiple types of solid tumor, but its effect on acute myeloid leukemia is less studied, and the underlying mechanisms still largely unknown. This study aimed to explore the specific target and potential mechanism of quercetin-induced cell death in AML. First, we found that quercetin induces cell death in the form of apoptosis, which was caspase dependent. Second, we found that quercetin-induced apoptosis depends on the decrease of mitochondria membrane potential (MMP) and Bcl-2 proteins. With quantitative chemical proteomics, we observed the downregulation of VEGFR2 and PI3K/Akt signaling in quercetin-treated cells. Consistently, cell studies also identified that VEGFR2 and PI3K/Akt signaling pathways are involved in the action of quercetin on mitochondria and Bcl-2 proteins. The decrease of MMP and cell death could be rescued when PI3K/Akt signaling is activated, suggesting that VEGFR2 and PI3K/Akt exert as upstream regulators for quercetin effect on apoptosis induction in AML cells. In conclusion, our findings from this study provide convincing evidence that quercetin induces cell death via downregulation of VEGF/Akt signaling pathways and mitochondria-mediated apoptosis in AML cells.

The present study was conducted to assess the efficacy of a plant extract (PE) on growth performance and immune status in foot and mouth disease (FMD)-vaccinated growing pigs. A total of 120 crossed ((Landrace × Yorkshire) × Duroc) growing pigs with an average initial body weight (BW) of 24.66 ± 2.34 kg and an average age of 70 days were randomized into three groups (10 pens; 4 pigs per pen per treatment) as follows: a nonvaccinated negative control group (NV), a FMD vaccinated group (OV), and a third group received a 0.0125% PE supplement after vaccination (PV), in a 6-week trial. The PV group receiving PE supplementation increased (p < 0.05) the BW compared with the OV group, and average daily gain (ADG) during days 1−14, overall and gain-to-feed ratio (G: F) in days 1−14, and dry matter (DM) digestibility at week 6 were higher (p < 0.05) in the PV compared with the OV group. A significant increase (p < 0.05) in haptoglobin concentration was observed in the OV group compared with the NV group at 25 days postvaccination. The inhibition percentage of antibodies against FMD in the sera reached above 50% in the PV group 5 days earlier than in the OV group. The findings suggest that the inclusion of PE in the diet promoted the performance of vaccinated growing pigs.

Mapping major quantitative trait loci (QTL) responsible for rice seed germinability under low temperature (GULT) can provide valuable genetic source for improving cold tolerance in rice breeding. In this study, 124 rice backcross recombinant inbred lines (BRILs) derived from a cross indica cv. Changhui 891 and japonica cv. 02428 were genotyped through re-sequencing technology. A bin map was generated which includes 3057 bins covering distance of 1266.5 cM with an average of 0.41 cM between markers. On the basis of newly constructed high-density genetic map, six QTL were detected ranging from 40 to 140 kb on Nipponbare genome. Among these, two QTL qCGR8 and qGRR11 alleles shared by 02428 could increase GULT and seed germination recovery rate after cold stress, respectively. However, qNGR1 and qNGR4 may be two major QTL affecting indica Changhui 891germination under normal condition. QTL qGRR1 and qGRR8 affected the seed germination recovery rate after cold stress and the alleles with increasing effects were shared by the Changhui 891 could improve seed germination rate after cold stress dramatically. These QTL could be a highly valuable genetic factors for cold tolerance improvement in rice lines. Moreover, the BRILs developed in this study will serve as an appropriate choice for mapping and studying genetic basis of rice complex traits.

At present, the management of Phytophthora capsici (P. capsici) mainly relies on chemical pesticides. However, along with the resistance generated by P. capsici to these chemical pesticides, the toxicity and non-degradability of this chemical molecule may also cause serious environmental problems. Herein, a new bio-based nano-antifungal material (CNC@CTAB) was made with coating hexadecyl trimethyl ammonium bromide (CTAB) on the surface of a cellulose nanocrystal (CNC). This material was then applied to the prevention of P. capcisi. This particle was facilely fabricated by mixing CTAB and sulfuric group modified CNC in an aqueous solvent. Compared to pure CTAB, the enrichment of CTAB on the CNC surface showed a better anti-oomycete activity both in vitro and in vivo. When CNC@CTAB was applied on P. capsici in vitro, the inhibition rate reached as high as 100%, while on the pepper leaf, the particle could also efficiently prevent the infection of P. capsici, and achieve a disease index as low as zero Thus, considering the high safety of CNC@CTAB in agricultural applications, and its high anti-oomycete activity against P. capsici, we believe that this CNC@CTAB has great application potential as a new green nano-fungicide in P. capsici management during the production of peppers or other vegetables.

The detection of proteins is of great biological significance as disease biomarkers in early diagnosis, prognosis tracking and therapeutic evaluation. Thus, we developed a simple, sensitive and universal protein-sensing platform based on peptide and graphene oxide (GO). The design consists of a fluorophore (TAMRA, TAM), a peptide containing eight arginines and peptide ligand that could recognize the target protein, and GO used as a quencher. To demonstrate the feasible use of the sensor for target detection, Bcl-xL was evaluated as the model target. The sensor was proved to be sensitive and applied for the detection of the target proteins in buffer, 2% serum and living cells.

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